The aim of this project is to study, at the molecular level, the events involved in immunoglobulin Ig heavy chain CH class switching as well as a mechanism by which T cells regulate such switching. In initial studies we sought a cellular system which would allow us to study B cell isotype differentiation employing clonal T cells and clonal B cell populations. Ultimately, we found that the B cell lymphoma 70Z/3 and the B cell lymphoma M12.4.1 can be induced to undergo isotype differentiation by a Peyer's patch-derived T cell hybridoma, HAJ 3. In studies of 70Z/3 B cells it was found that the Z02/3 B cells expressed small amounts of membrane IgM (mIgM) and no membrane IgG (mIgG) prior to culture, whereas these B cells expressed large amounts of mIgGM and mIgG2b following co-culture with HAJ-3 T cells. Such new Ig expression is associated with the induction of IgG2b specific mRNA, but not with DNA switch region rearrangement or CH deletion. The effect of LPS is quite different in that it stimulates 70Z/3 B cells to express considerable amounts of IgG2b mRNA, but does not induce expression of detectable mIgG2b; this indicates that a T cell influence is necessary for the production of translatable IgG2b mRNA. In studies of M12.4.1 cells we found that M12.4.1 B cells constituentively express mIgG2a, but upon co-culture with HAJ-3 T cells the mIgG2a disappears and mIgM and mIgG2b are induced. This induction is not associated with DNA recombination on deletion in that re-culture of induced M12.4.1 B cells in the absence of T cells leads to disappearance of mIgM and mIgG2b and then re-appearance upon re-cultured with HAJ-3T cells. Finally, molecular analysis of T cell-induced M12.4.1 B cell expression of mIgM indicates that the latter is associated with nascent production of -specific mRNA synthesis. In all, these results are consistent with the idea that the first step of a B cell isotype differentiation is a reversible, T cell-induced step in which downstream gene transcription and translation is brought about in the absence of switch recombination and deletion.